The present invention encompasses articles designed to provide substantially immediate release of a desirable material present on the outside of the articles, and during a subsequent time period to provide controlled release of surfactant compounds contained within the articles. More specifically, the articles herein are characterized by a container having any desired material (e.g., a biologically active agent) releasably affixed on the outer surface, said container releasably enclosing a solution of a micelle-forming surfactant compound which can migrate from the container via a microporous membrane.
The desirability of providing metered dosage forms of biologically active or medicinal agents has long been recognized. Metered dosages can be manifest either as "controlled release" or "sustained release" of a given material. The distinction between controlled release and sustained or prolonged release has been recognized; see Cowsar, in "Advances in Experimental Medicine and Biology", Vol 49, "Controlled Release of Biologically Active Agents", Ed. Tanquary and Lacey, Plenum Press, New York 1974.
The copending application of R. G. Laughlin, entitled CONTROLLED RELEASE ARTICLES, filed Mar. 19, 1975, Ser. No. 560,020, now abandoned, the disclosures of which are incorporated herein by reference, succinctly describes controlled release and sustained release articles. The application also discloses controlled release articles comprising a micelle-forming surfactant and a microporous membrane of the type employed in the improved articles herein.
Briefly stated, controlled release articles respond rapidly to changes such as dilution effects in the environment external to the article, e.g., by body fluid changes, whereas sustained release articles do not. The net result is that articles based on the principle of controlled release are capable of rapidly establishing an effective level or concentration of a medicament or other agent in a selected environment, and then shutting off release so as to maintain the concentration at that level. In contrast, sustained release articles simply dispense an agent at a constant rate and do not display the feedback regulation of release that a controlled release article displays.
It will be appreciated that articles operating by the controlled release mechanism provide substantial advantages over sustaining release articles for certain uses. For example, placement of a properly formulated controlled release medicament system in an animal's body cavity in contact with body fluids establishes and maintains an effective concentration of the medicament in the fluids. The system responds to dilution or depletion as additional fluids are secreted, or the medicament is bound to tissue, absorbed, etc., thereby automatically maintaining the concentration of medicament at the proper level.
A controlled release article requires an initial period of time to establish an effective concentration of the agent being released in the environment external to the article. This time lapse may be unacceptable; for example, in vaginal contraceptives it may be important to provide an effective amount of a contraceptive agent immediately. The present invention provides a solution to this problem.
As disclosed in the application of Laughlin, above, solutions of micelle-forming surfactant compounds can be releasably enclosed in a container comprising a microporous membrane. Articles prepared in this manner are stable and do not suffer osmotic rupture when placed in body cavities in contact with body fluids. Rather, the stable articles provide controlled release of the surfactant into the body fluids. The proper selection of surfactant provides a means for achieving various biological effects, e.g., antimicrobial activity, spermicidal activity, and the like. Such articles can be used in any situation where controlled release of a surfactant into an external fluid medium is desired and, while especially useful in body cavities such as the vagina, are not limited to such use.
By the present invention the foregoing type of article is provided with an outer layer or coating of and agent (which need not be a surfactant) which is immediately released on contact with the environment in which the article is placed, e.g., a body cavity. A quantity of this outer agent sufficient to provide the desired response is therby provided immediately. Controlled release and maintenance of an effective amount of the surfactant then ensues.
The following United States patents relate to articles comprising drugs enclosed with permeable membranes: U.S. Pat. No. 3,828,777 MICROPOROUS OCULAR DEVICE, issued Aug. 13, 1974 to R. A. Ness; U.S. Pat. No. 3,618,604 OCULAR INSERT, issued Nov. 9, 1971 to R. A. Ness; U.S. Pat. No. 3,416,530 EYEBALL MEDICATION DISPENSING TABLET, issued Dec. 17, 1968 to R. A. Ness; U.S. Pat. No. 3,832,252 METHOD OF MAKING A DRUG-DELIVERY DEVICE, issued Aug. 27, 1974 to T. Higuchi and H. M. Leeper. (See also U.S. Pat. No. 3,598,122, issued 10/1971, other references cited in Higuchi, et al., as well as U.S. Pat. No. 3,867,519.)
In general, the foregoing references relate to sustained release articles, rather than controlled release articles. The Higuchi, et al., patent illustrates the use of internal barriers in an article to achieve sustained drug release in the manner noted hereinabove. None of the references suggest the present articles which provide both immediate and controlled release of desirable agents.
Attwood and Florence, J. Pharm. Pharmac., 1971, 23, Suppl. 242S, briefly describe the dialysis of chlorpromazine across Visking membranes and suggest that this phenomenon may have applications in sustained release technology.. Attwood, et al., do not suggest articles of the present type.
Lichtman, et al., Contraception 8 (4) 291-7 (1973) describe a vaginal contraceptive device comprising a soluble film containing a nonionic surfactant as a spermicide.
U.S. Pat. No. 3,694,364 LAUNDERING AID, issued Sept. 26, 1972 to J. B. Edwards, relates to surface-modified cellulose bags (e.g., terry cloth) containing detergents and their use in laundry baths.